The objective of this project is to study the chemistry and biology of a newly discovered mitogenic growth factor polypeptide which is transported in human blood by platelets. This plateletderived growth factor (PDGF) polypeptide has been recently purified to homogeneity. It is heat stable (100~C) and has an isoelectric point of about 9.8. Unreduced PDGF has a molecular weight of about 35,000 and consists of two inactive polypeptide chains held together by disulfide bonds. The amino-terminal amino acid sequence of PDGF has been recently elucidated. PDGF represents the major polypeptide growth factor of human serum. It is a potent mitogen and is indispensable for the growth of connective tissue cells in culture. In addition to its mitogen activity, PDGF stimulates cell migration and regulates cellular metabolism, including protein, lipid and prostaglandin synthesis. Anti-PDGF antisera produced in rabbits were shown to completely neutralize the biological activities of PDGF. Radioreceptor assays for PDGF have shown the presence of specific membrane receptors in target cells. It is postulated that the initial event in the action of PDGF is its interaction with the specific receptor. Unlike normal cells, viral-transformed cells and certain human malignant cells in culture do not require PDGF for growth. The transformed and malignant cells appear to produce their own growth-promoting factors which promote their uncontrolled growth, escaping the regulatory need for PDGF. A human osteosarcoma cell line has been identified that produces a PDGF-like polypeptide with properties and activities similar to those of PDGF. Antisera to human PDGF completely neutralized the mitogenic activity of the osteosarcoma-derived PDGF polypeptide.